This invention relates to a novel oral pharmaceutical formulation of indomethacin having controlled release properties.
The formulation is directed to a coated pellet from which a pharmaceutical compound is slowly released over time. This formulation has been shown to exhibit excellent controlled release properties. The formulation provides an immediate release indomethacin for elevating blood levels to pharmacologically effective levels and sustained release indomethacin for maintaining those levels.
It has long been known that almost all pharmacologically active compounds are most effective when present in plasma within a certain concentration range. Above this range, there sometimes may be a danger that deleterious side effects may become manifest and even when there is not the danger, excess drug in the blood plasma may be wasted if the concentration is significantly above the blood level that results in the maximum pharmacological effect. Below this range, there often may be a danger that the active agent may not be maximally effective or even effective at all.
An oral dosage form is the preferred route of administration of pharmaceutical compounds because it provides easy, low cost administration. However, patient compliance becomes an important factor to consider in conjunction with oral administration of a pharmaceutical compound, especially if the compound must be taken three or four times a day. To maximize patient compliance, here, one attempts to reduce the number of dosage forms a patient must take to attain effective therapy, while at the same time provide an oral dosage form which is palatable to the patient.
One method of accomplishing this goal is the use of sustained release formulations which have been numerously described in the prior art. Many of these formulations are comprised of a solid, polymeric matrix throughout which a pharmaceutical compound has been dispersed. After the formulation is ingested, the active pharmaceutical compound will slowly release from the polymer matrix, resulting in prolonged release of the active agent.
The indomethacin controlled release formulations of the present invention comprise a capsule including coated pellets which exhibit both immediate release and sustained release characteristics in the same capsule. The immediate release of indomethacin provides elevated blood levels within about 2 hours after ingestion. The sustained release maintains the blood levels of indomethacin for longer periods of time than the prior art compounds.
Indomethacin has been the most successful non-steroidal anti-inflammatory agent available for the treatment of rheumatoid arthritis, osteoarthritis, as well as other anti-inflammatory diseases. The administration of indomethacin in traditional capsule or tablet form, to maintain effective blood levels of active agent, requires the ingestion of a capsule three or four times a day. Most patients being treated on this drug regimen are elderly and often must take several other capsules or tablets for the treatment of other conditions or disease states. Accordingly, it is important for the convenience of the patient and to ensure compliance that the frequency of administration be kept to a minimum.
It is also important to maintain a continuous anti-inflammatory serum concentration of indomethacin. This is particularly difficult to accomplish with the traditional pharmaceutical forms of indomethacin which are rapidly absorbed. These traditional forms result in initial high plasma concentrations of indomethacin which are then slowly metabolized to low blood levels. The length of time that indomethacin blood levels are at effective concentrations is far from optimal.
It is therefore an object of this invention to provide a pharmaceutical composition of indomethacin with both sustained release properties and rapid release properties in one capsule which is orally active. It is a further object of this invention to provide plasma concentrations of indomethacin which are pharmacologically effective for the longest duration of time.
It is a further object of this invention to provide a controlled release capsule of indomethacin that can be administered only once a day.
It is also an object of this invention to provide a method for producing the novel sustained release formulation of this invention.